STUDIO DI PATOLOGIE GENETICHE E CARATTERI DI INTERESSE A BASE EREDITARIA NEGLI ANIMALI D'AFFEZIONE

Primary hypertrophic cardiomyopathy (HCM) is the most common cardiac disease in cats and humans, characterized by an impressive phenotypic and genotypic heterogeneity. Autosomal dominant inheritance and two causative mutations in cardiac myosin binding protein C 3 gene (MYBPC3), at position A31P and R820W, were respectively identified in Maine Coon and Ragdoll cats with HCM. Beyond the reported Maine Coon and Ragdoll mutations, A74T, another single nucleotide polymorphism (SNP) in MYBPC3, was suspected to cause HCM in Maine Coon. In the present work, HCM-associated mutations have been genotyped by direct sequencing in 741 Italian cats examined through standardized ultrasound. The prevalence of the mutations and their correlation with the disease in Maine Coon and Ragdoll cats have been calculated. In one more focused cohort of 393 samples, the MYBPC3 region including A31P and A74T loci it has been analyzed more in detail. Multiple alignment have been performed clustering samples by different breeds and several “geno-variants” have been recorded. Future research will be directed to apply high density array (75.000 SNPs) to the research on feline hypertrophic cardiomyopathy, aiming at identifying more mutations in the affected animals and at evaluating their association with the developments of the disease. X-linked progressive retinal atrophy 2 (XLPRA2) is a severe, early-onset, and progressive rod and cone disease of dogs, caused by a 2 bp microdeletion in RPGRORF15. This study provides a list of the relevant DE miRNAs associated with retinal degeneration and disease progression in XLPRA2-mutant retinas at the most relevant disease-related ages: before (3 wks), during (7 wks), and after (16 wks) the peak of photoreceptor death, to further examine their role in retinal development and in RPGRORF15 mutant retinas. Expression profiles of age-matched 3, 7, and 16 wks old normal and XLRPA2-mutant retinas (3/age/group) were analyzed using miRNA-specific Affymetrix microarrays (46,228 probes/7,815 probe sets/177 canine specific). To confirm the data obtained from the array, quantitative real-time PCR of miR-183, miR-155, miR-146a, miR-129, miR-29b, and miR-19a was performed. Future research will be directed to real-time PCR validation of additional DE miRNAs, in vitro analysis at the protein level, integration with recently published transcriptomic data10, and comparison with other similar retinal degenerative diseases (e.g. rcd1) in order to determine if the DE miRNAs are disease-specific, or common to several early onset retinal degenerations.